Malignant Transformation of Plexiform Neurofibroma Due to Neglected Giant Soft Tissue Swelling of the Back: A Case Report.

Neurofibromatosis type 1 can be severe and associated with malignant transformation. Proper follow-up and monitoring are very important in preventing the malignant transformation of neurofibromatosis. We encountered a case of malignant transformation of plexiform neurofibroma into neurofibrosarcoma (also known as malignant peripheral nerve sheath tumor). She had been presenting with a large mass on her back for a few years, which was also associated with an ulcer. She underwent a wide-excision biopsy of her back, and the histopathology examination (HPE) came back with a malignant peripheral nerve sheath tumor. This case concludes that any patient with a known case of neurofibromatosis should undergo follow-up to detect any malignant transformation of the disease. Early detection of the malignant transformation of neurofibromatosis can help prevent the disease's progression. The main treatment is surgical resection; however, the risk of local recurrence is higher, especially in patients with neurofibromatosis type 1.

Contemporary surgical management of pediatric non-rhabdomyosarcoma soft tissue sarcoma.

Non-rhabdomyosarcoma soft tissue sarcoma (STS) comprises most STS in pediatric patients. It is a diverse set of over 30 histologic subtypes. Treatment is based on risk group determined by tumor size, grade, and the presence of metastases. Surgical resection is a cornerstone of therapy, as tumors are often resistant to chemotherapy or radiation. While patients with isolated tumors less than 5 cm may undergo upfront resection, strong consideration should be given to neoadjuvant chemoradiotherapy to ensure negative margins at surgical resection and optimal outcomes. Sentinel lymph node biopsy is strongly recommended for clear cell and epithelioid sarcomas. The most common metastatic site is the lung, and metastases should be resected at the end of therapy, when feasible. Unfortunately, many high-risk patients progress on therapy, and alternative strategies including earlier metastatic control require investigation.

A rare Encounter with Pediatric Malignant Peripheral Nerve Sheath Tumor in Nasal Sinuses and Orbit.

This case report explores a rare and aggressive Malignant Peripheral Nerve Sheath Tumor (MPNST) in a 7-year-old child affecting nasal sinuses, maxilla, and orbit, an exceptionally uncommon pediatric manifestation unrelated to Neurofibromatosis 1. The child presented with alarming symptoms-nasal obstruction, snoring, epistaxis, and difficulty swallowing-underscoring the case's urgency. Non-contrast computed tomography revealed an extensive mass infiltrating nasopharynx, nasal cavity, maxillary sinus, ethmoid sinuses, and orbit, causing destructive consequences. Histopathology confirmed a high-grade MPNST, marked by rapid growth and early metastasis, highlighting management challenges. The rarity of pediatric MPNST in the nasal cavity is discussed, emphasizing the need for a broad differential diagnosis. Treatment involves surgical resection and adjuvant chemoradiation with a grim prognosis due to diagnostic complexities and morphological mimicry in young patients.

Orbital malignant peripheral nerve sheath tumor: A case report and review.

Malignant peripheral nerve sheath tumor of the orbit is an exceedingly rare entity. These tumors exhibit locally aggressive behavior, recurrences, distant metastasis, and poor response to existing treatment protocols. Orbital nerve sheath tumors are often associated with neurofibromatosis 1, and malignant transformation of neurofibroma into malignant nerve sheath tumor has also been seen. The recommended treatment for localized disease is radical or wide surgical excision to achieve negative margins followed by chemoradiation. For extensive disease, chemotherapy and radiotherapy can be utilized to stabilize the disease. Due to poor response and outcomes with current regimens, the focus has been shifted to approaches utilizing molecular targets and immunological agents. Despite all the advancements, the outcomes still remain discouraging for moderate- to high-grade lesions and thus necessitate studies to design promising treatment modalities.

Denosumab combined with chemotherapy followed by anlotinib in the treatment of multiple metastases of malignant peripheral nerve sheath tumor: a case report and literature review.

Primary intraosseous malignant peripheral nerve sheath tumors (MPNSTs) are rare yet highly aggressive neoplasms originating from peripheral nerves. Typically manifesting as soft tissue masses accompanied by pain or functional impairment, these tumors pose significant challenges in management. Surgical intervention remains the cornerstone of treatment for patients with MPNST lacking distant metastasis, with generally modest success rates. In cases of recurrence and metastasis, the pursuit of effective systemic therapies has been a focus of clinical investigation. Herein, we present a case study involving an elderly female patient with refractory MPNST. In light of surgical limitations, a multimodal therapeutic approach combining chemotherapy, denosumab, and subsequent administration of anlotinib was pursued following collaborative consultation. This regimen yielded noteworthy clinical benefits, exemplifying a promising avenue in the management of challenging MPNST cases.

Nerve Sheath Myxoma in Pregnancy: A Case Report.

Nerve sheath myxoma (NSM) is a rare benign peripheral nerve sheath tumor that affects young adults. NSMs are asymptomatic, slow-growing swellings located in the upper extremities, more rarely in the lower extremities. Given the high risk of recurrence, it is recommended to perform a complete exeresis. To our knowledge, the evolution and management of NMS during pregnancy have not been described yet. We report the first case of recurrent pretibial NSM in a pregnant girl and its follow-up and outcome during and after pregnancy. NSM is difficult to diagnose clinically or using imaging. The final diagnosis remains histopathological. It is known how various types of benign and malignant skin tumors can develop or change during pregnancy. With our case, however, we documented that pregnancy does not affect the growth and evolution of NSM. Given the benign nature of the lesions and their tendency to grow slowly, during pregnancy, follow-up of NSMs can be conducted through ultrasonography and surgical treatment postponed after delivery. Our case highlights the importance of careful monitoring and individualized decision making, especially in rare scenarios such as NSM, where data on the progression of benign lesions are limited. Our case highlights the importance of a careful monitoring and a tailored treatment in rare scenarios such as NSM, where data on the progression of benign lesions are limited. Considering the benign nature of the lesions and their tendency to grow slowly, follow-up of NSMs during pregnancy can be conducted through ultrasonography, and surgical treatment can be postponed after delivery.

Primary BAP1-absent atypical meningioma arising from median nerve within infraclavicular brachial plexus: illustrative case.

BACKGROUND: The authors present the only known case of a World Health Organization grade II ectopic meningioma occurring in the infraclavicular brachial plexus, causing pain within the axilla not associated with a primary malignant meningioma of the central nervous system. Peripheral nerve sheath tumors are rare entities, the majority of which are schwannomas or neurofibromas. Ectopic meningiomas only represent 1%-2% of all meningiomas. To date, there is one other published case specifically of a primary ectopic meningioma located in the brachial plexus. OBSERVATIONS: Following the dissection of the left axilla, a dominant rubbery tumor involving the median nerve was encountered. The tumor capsule contained areas of hemorrhage and a soft core with nerve fascicles coursing through, which were not compromised during internal tumor debulking. The tumor lacked a clear pseudocapsule that is characteristically seen in schwannomas. Histopathological studies confirmed an atypical epithelioid neoplasm with elevated numbers of mitotic figures and BAP1 gene deletion. LESSONS: Primary meningiomas arising outside the central nervous system are exceedingly rare. For this unusual higher-grade primary ectopic meningioma located in the distal brachial plexus, surgery with the goal of gross-total resection, adjuvant radiation, additional imaging, and genetics screening were recommended. Close follow-up is warranted. https://thejns.org/doi/10.3171/CASE24226.

Rare primary intrapulmonary malignant peripheral nerve sheath tumor showing significant response to sintilimab: A case report and literature review.

Primary pulmonary malignant peripheral nerve sheath tumor (MPNST) is a rare soft tissue sarcoma with a low incidence, poor prognosis and limited treatment options. The present study reported a case of lung MPNST in a 63-year-old male patient without any pulmonary symptoms. Immunohistochemical analysis of the tumor indicated a programmed death-ligand 1 (PD-L1) expression tumor proportion score of 60%. A total of six courses of sintilimab were used in this patient and a remarkable response was achieved. In summary, sintilimab single-agent immunotherapy may be a novel treatment for pulmonary MPNST. When encountering analogous cases in the future, oncologists can test for the expression of PD-L1 in patients to guide the therapy's design.

TRPS1 expression in MPNST is correlated with PRC2 inactivation and loss of H3K27me3.

Initially described as a highly specific immunohistochemical marker for carcinomas of mammary origin, trichorhinophalangeal syndrome type 1 (TRPS1) has subsequently been detected in a variety of other non-mammary tumors. In this study, we examined the immunohistochemical expression of TRPS1 in 114 peripheral nerve sheath tumors, including 43 malignant peripheral nerve sheath tumors (MPNSTs), 58 schwannomas, including 9 cellular neurofibromas, and 13 neurofibromas, including 1 atypical neurofibroma. Notably, TRPS1 was expressed in 49% of MPNSTs and was absent in all schwannomas and neurofibromas. All MPNSTs showed TRPS1 labeling in >50% of nuclei, with 95% of cases demonstrating diffuse labeling. Most cases (67%) showed weak TRPS1 immunoreactivity, while a smaller subset showed moderate (24%) or strong (9%) intensity staining. Analysis of publicly available gene expression datasets revealed higher levels of TRPS1 mRNA in MPNSTs with PRC2 inactivation. In keeping with this finding, TRPS1 expression was more commonly observed in MPNSTs with loss of H3K27me3, suggesting a potential relationship between TRPS1 and the PRC2 complex. This study further broadens the spectrum of TRPS1-expressing tumors to include MPNST.

Common Benign Nerve Sheath Tumor at an Uncommon Location - Gastric Schwannoma.

Gastric schwannomas are rare types of gastrointestinal mesenchymal tumours that are slow-growing and mostly benign. They are usually asymptomatic. In some cases, nonspecific gastric symptoms, palpable mass, and bleeding can be seen. A definitive diagnosis requires pathological and immunohistochemical examination, and surgical resection offers an excellent prognosis with uncommon recurrence. We present a case of a 62-year-old woman who underwent exploratory laparotomy and wedge resection with preoperative diagnosis as gastrointestinal stromal tumor and postoperatively diagnosed as schwannoma on histopathology.

Outcomes of Head and Neck Neurogenic Tumors.

BACKGROUND: Lateral neck mass management frequently challenges surgeons. Nerve tissue neoplasms are an uncommon cause of such nodules. Neurogenic tumors form a tiny percentage of the head and neck neoplastic lesions. Considering the number of nerves in this area, it is surprising that such neoplasms are not more frequently seen. METHODS: A retrospective study was conducted on all patients who presented to the National Cancer Institute of Cairo, Egypt, with head and neck neurogenic neoplasms. RESULTS: During the last 10 years at the National Cancer Institute of Egypt (2006-2015), 40 cases of neurogenic tumors of the head and neck were treated at the head and neck unit. Patients' ages ranged from two to 78 years with a mean age of 34.7 years. Childhood neurogenic tumors accounted for nine cases (22.5%) only in this study. Male patients diagnosed with these tumors comprised 16 cases, while female patients comprised 24 cases, with a female-to-male ratio of 1.5:1. Patient presentation depends on the biological behavior of the tumor; for instance, some of them present by slowly growing painless well-circumscribed mobile swelling, and others present by rapidly growing swelling with neurological deficit. Clinical picture and imaging studies such as CT and MRI raise suspicion and may help delineate such tumors, but a definitive diagnosis is obtained by tissue biopsy. Surgery is the mainstay of treatment in most head and neck neurogenic tumors, whereas adjuvant therapy is of limited benefit in some types of neurogenic tumors. The five-year survival rate was 60% for the malignant group, while death was reported in six out of 15 cases (40%).  Conclusion: Most neurogenic head and neck tumors are benign. Accurate preoperative assessment and a high degree of suspicion are the initial steps in the management. Proper treatment involves complete surgical excision; however, debulking procedures have an important role. Malignant neurogenic tumors are aggressive and are treated with combined radical surgical resection and radiation. Chemotherapy is tried for locally advanced unresectable or metastatic disease.

Forelimb lameness caused by malignant peripheral nerve sheath tumors of the median nerve in a dog: a case report.

An 8-year-old Portuguese Water Dog presented with a 5-month history of left forelimb lameness. There was palmar pain. Ultrasonography revealed enlargement of the left median nerve. Subsequent MRI also showed enlargement of the median nerve in the distal palmar to the mid-forearm region. Rapid intraoperative diagnosis suggested malignant peripheral nerve sheath tumors (MPNST) and a neurotomy was performed. The lameness had almost disappeared in 1 month after surgery. Recurrence occurred 26 months postoperatively and the forelimb was amputated. At 950 days after the neurotomy, radiography revealed lung metastasis, and the dog died 988 days after the neurotomy. Neurotomy for MPNST should be performed with caution until more information is available regarding methods for early detection, margin determination, and indication determination for neurotomy.

Long-term Follow-up with MRI Scans After Enucleation of Peripheral Nerve Schwannomas: Results from a Single-center Case Series.

BACKGROUND: Enucleation is a surgical technique to resect peripheral nerve schwannomas. The procedure has a low risk for postoperative deficit, but a small chance for recurrence, because tumor cells may remain inside the pseudocapsule that is left after resection. Magnetic resonance imaging (MRI) scans are frequently performed after surgery to investigate potential residual tumor, but currently there is little information in the literature on the value of follow-up with MRI. MATERIAL AND METHODS: All patients who underwent enucleation of a peripheral nerve schwannoma between October 2013 and June 2022 were included. Postoperative MRI scans (gadolinium-enhanced) made at different time points after the surgery were re-examined for residual enhancement. Patients with residual enhancement were contacted to inform whether symptoms had recurred. RESULTS: A total of 75 schwannoma enucleations in 74 patients were included. The first postoperative MRI scan, performed 3 months after the surgery, showed no residual enhancement in 50 patients. In the remaining 24 patients, another MRI scan was made 1 year after the surgery, which still showed a possible remnant in 11 patients. On the third MRI scan, performed 2 years after enucleation, there were 7 suspected cases (9%). None of these patients had clinical symptoms at a mean postoperative follow-up of 5 years. CONCLUSIONS: Our data show that the value of postoperative MRI scans after enucleation of peripheral nerve schwannomas is limited, because residual enhancement in the beginning can be non-specific and the small percentage of patients, that persistently had a potential remnant, were all asymptomatic.

High-Grade Malignant Peripheral Nerve Sheath Tumor Arising From Common Peroneal Nerve Neurofibroma.

This article presents a case report of a 45-year-old male with neurofibromatosis type I (NF1) who developed a high-grade malignant peripheral nerve sheath tumor (MPNST) originating from a neurofibroma within the common peroneal nerve over popliteal fossa. MPNSTs are aggressive tumors associated with NF1, causing significant mortality. The patient underwent tumor resection surgery and received postoperative radiation therapy. Follow-up examinations showed no impairment of motor function and no tumor recurrence after regular MRI evaluation for four years. This article explores the challenges of distinguishing benign neurofibromas from malignant MPNST via MRI image and biopsy, and achieving a balance between tumor excision and preserving nerve functionality during surgical treatment. However, caution is warranted due to the risk of recurrence.

Enhanced IL-12 transgene expression improves oncolytic viroimmunotherapy.

Introduction: Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive sarcomas with unacceptably low cure rates occurring often in patients with neurofibromatosis 1 defects. To investigate oncolytic Herpes Simplex Virus (oHSV) as an immunotherapeutic approach, we compared viral replication, functional activity, and immune response between unarmed and interleukin 12 (IL-12)-armed oncolytic viruses in virus-permissive (B109) and -resistant (67C-4) murine MPNSTs. Methods: This study compared two attenuated IL-12-oHSVs with γ134.5 gene deletions (Δγ134.5) and the same transgene expression cassette. The primary difference in the IL-12-oHSVs was in their ability to counter the translational arrest response in infected cells. Unlike M002 (Δγ134.5, mIL-12), C002 (Δγ134.5, mIL-12, IRS1) expresses an HCMV IRS1 gene and evades dsRNA activated translational arrest in infected cells. Results and discussion: Our results show that oHSV replication and gene expression results in vitro were not predictive of oHSV direct oncolytic activity in vivo. Tumors that supported viral replication in cell culture studies resisted viral replication by both oHSVs and restricted M002 transgene expression in vivo. Furthermore, two IL-12-oHSVs with equivalent transcriptional activity differed in IL-12 protein production in vivo, and the differences in IL-12 protein levels were reflected in immune infiltrate activity changes as well as tumor growth suppression differences between the IL-12-oHSVs. C002-treated tumors exhibited sustained IL-12 production with improved dendritic cells, monocyte-macrophage activity (MHCII, CD80/CD86 upregulation) and a polyfunctional Th1-cell response in the tumor infiltrates. Conclusion: These results suggest that transgene protein production differences between oHSVs in vivo, in addition to replication differences, can impact OV-therapeutic activity.

Images in Immunotherapy and Precision Oncology: A Case Report of Neurofibromatosis-1.

Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder that primarily causes the growth of tumors along nerves. Additionally, the germline mutations involved in NF1 predispose patients to develop further malignancies. The mainstay initial treatment for these malignancies is surgical removal at diagnosis, although targeted therapies are under evaluation in the relapsed setting. We report a case of malignant peripheral nerve sheath tumor (MPNST), gastrointestinal stromal tumor (GIST), and pheochromocytoma in a patient with NF1 who presented with an infected right shoulder lesion that was confirmed to be spindle cell sarcoma via biopsy. She was treated with antibiotics; however, she rapidly deteriorated and opted for hospice care. NF1 germline mutations increase the risk of patients developing various types of cancer. Recent studies have shown that there is a role for using MEK inhibitors such as selumetinib for treating patients with NF1.

Peripheral nerve tumors.

The chapter is focused on the neoplastic peripheral nerve lesions, which primarily involve "cranial and paraspinal nerves," as outlined in the CNS volume (WHO_Classification_of_Tumours_Editorial_Board, 2021). These include classic peripheral nerve sheath tumors such as schwannoma, neurofibroma, intraneural perineurioma, and malignant peripheral nerve sheath tumors, with their variants as well as new and more precisely defined entities, including hybrid nerve sheath tumors and malignant melanotic nerve sheath tumor (previously melanotic schwannoma).

Decorin suppresses stemness and migration potential of malignant peripheral nerve sheath tumor through inhibiting epidermal growth factor receptor signaling.

Cancer stem cells (CSCs) play pivotal roles in the growth, invasion, metastasis, chemo-resistance in malignant peripheral nerve sheath tumor (MPNST). The current characterization of CSCs in MPNST is not complete. Decorin is a critical regulator of microenvironment, but its expression and function in CSCs of MPNST has not been studied. In the current study, Decorin levels and its relationship with lung and liver metastasis were determined in clinical specimens. Decorin expression in CD133-positive or CD44-positive CSCs was analyzed by RT-qPCR on cytospun MPNST cells after flow cytometry-based cell sorting. Decorin-positive cells were separated from Decorin-negative cells in transfected MPNST cell lines using a designed plasmid expressing red fluorescent protein (RFP) under a Decorin promoter. Tumor sphere formation, tumor growth, cell invasion, cell migration, and the resistance to chemotherapy-induced apoptosis were determined on Decorin-positive versus Decorin-negative MPNST cells. In vivo tumor growth was analyzed in mice receiving subcutaneous transplantation of Decorin-positive versus Decorin-negative MPNSTs. We found that Decorin levels were significantly downregulated in MPNST specimens, compared to non-tumorous adjacent tissue. Significantly lower Decorin levels were detected in MPNSTs with lung or liver metastasis compared to those without. Poorer patient survival was detected in Decorin-low MPNST, compared to Decorin-high subjects. More Decorin-negative cells were detected in CD133-positive MPNST cells than CD133-negative MPNST cells, and in CD44-positive MPNST cells than in CD44-negative MPNST cells. Compared to Decorin-positive MPNST cells, Decorin-negative MPNST cells generated significantly more tumor spheres in culture, were more invasive and migratory, and were more resistant to chemotherapy-induced apoptosis, likely due to the inhibition of epidermal growth factor receptor signaling by Decorin. Decorin-negative MPNST cells grew significantly larger tumor in vivo. Thus, depletion of Decorin may occur in CSCs in MPNSTs, serving possibly as a new therapeutic target.

Feline Facial Spindle Cell Tumors in 29 Cats: Histomorphological and Immunohistochemical Characterization.

Soft tissue tumors/sarcomas (STSs) in felines, encompassing a variety of mesenchymal tumors with similar histomorphological features, present diagnostic challenges due to their diverse cellular origins and the overlap with other tumor types such as feline sarcoid. This study aimed to delineate the clinical, histomorphological, and immunohistochemical characteristics of 34 feline facial spindle cell tumors affecting 29 cats, including testing for bovine papillomavirus type 14 (BPV14), the virus causing feline sarcoids. Only five out of 12 tumors previously diagnosed as feline sarcoids based on histomorphology were confirmed by PCR for BPV14, underscoring the importance of comprehensive diagnostic approaches to accurately distinguish between STSs and feline sarcoids. This study shows that most facial spindle cell tumors were compatible with peripheral nerve sheath tumors (PNSTs) based on positive immunohistochemical staining for Sox10 and other immunohistochemical markers such as GFAP, NSE, and S100. Some of these tumors displayed as multiple independent masses on the face or as erosive and ulcerative lesions without obvious mass formation, an atypical presentation and an important highlight for general practitioners, dermatologists, and oncologists. This study also describes periadnexal whorling of neoplastic cells as a novel histomorphologic finding in feline facial PNSTs and emphasizes Sox10 as a useful complementary immunohistochemical marker for the diagnosis of facial PNST in cats, providing valuable insights for veterinary pathologists.